The studies proposed are designed to identify the parameters predicting for the response of tumors to anticancer chemotherapy. It is now recognized that the response of the individual cell of antitumor agents may be determined by a number of factors. At the level of the target cell these include: pharmacodynamic factors reflected in drug uptake, retention, and efflux; metabolic factors reflected in drug activation and/or degradation, in utilization of de novo versus salvage pathways of DNA synthesis, in the formation of competing or reversing metabolic pools, in the turnover of target macromolecules and in the regulatton of cell kinetics. In the tumor taken as an organ drug delivery to the target cell may be affected by intratumor hemodynamic and other vascular factors. In the organism as a whole drug delivery to the cell will be influenced by a number of pharmacokinetic parameters. There are thus a large number of parameters which could determine the response of the tumor to drug therapy in an individual patient, though not all of these will be operative with all types of antitumor agent or of tumors. Therefore, this program represents an integrated multifactorial approach in which pharmacokinetic, cell kinetic, pharmacodynamic and biochemical parameters will be measured and integrated to produce a profile predictive for response in the individual patient. The study will be carried out with standard agents (Ara-C, MTX, Adriamycin) in leukemia, lung cancer undergoing resection and in solid tumors with accessible tumor for biopsy. It will be extended to newer drugs and to a study of drug interactions. An intensive investigation will also be carried out of the problems of tumor tissue sampling and handling and on those of tumor cell heterogeneity, viability and variability of response among cell subsets. The methods to be used include drug assays by radioactivity, high pressure liquid chromatography/HPLC), and enzyme inhibition determination of nucleotide pools by HPLC and determination of cell kinetic parameters by autoradiography. Data analysis and integration will be carried out using a DEC 10 and a Univac VMOS 70 computer.